ChemComm View Article Online
Published on 01 April 2015. Downloaded by UNIVERSITY OF NEBRASKA on 13/04/2015 15:21:04.
COMMUNICATION
Cite this: DOI: 10.1039/c5cc02000j Received 9th March 2015, Accepted 1st April 2015
View Journal
Stereoselective synthesis and reaction of gold(I) (Z)-enethiolates† Kazunori Miyamoto,*ab Masaya Hirobe,c Masanobu Uchiyamaab and Masahito Ochiaic
DOI: 10.1039/c5cc02000j www.rsc.org/chemcomm
Bench-top-storable (Z)-enethiol reagents: gold (Z)-1-decenylthiolates were synthesized stereoselectively in high yields. They are stable upon storage at room temperature without protection from light, and react smoothly with various alkyl halides, a,b-unsaturated ketones, and electron-deficient aryl halides with excellent stereoselectivity.
The (Z)-vinylthio moiety is an important functional group in organic synthesis and medicinal chemistry, being present in many pharmaceutically important compounds (Scheme 1).1,2 For example, a vinylthio functionality is present as a side chain in clavulanic acid derivatives, which show b-lactamase-inhibitory activity,1a and cephem derivatives, which exhibit broad-spectrum antibacterial activities.1b In both cases, the (Z)-isomers show greater activity than the (E)-isomers. The parent enethiols (RCHQCHSH) 1 are fairly tautomerically stable,3 but in general, they are thermally unstable and readily undergo dimerization to give dithiohemiacetals or divinylsulfides even at room temperature.4 Therefore, regio- and stereoselective synthesis of functionalized vinylthio moieties remains a challenging issue in organic synthesis, and only limited success has been achieved by using silyl vinyl sulfides as precursors.5,6 In contrast, some heavier-metal enethiolates are less prone to dimerization. For example, cesium (Z)-enethiolate generated in situ at low temperature reacts with alkyl halides to afford (Z)-vinyl sulfides with high stereoselectivity (up to 98 : 2).7 However, the use of a harder counter cation such as the lithium ion results in configurational lability: enethiolate 1a (R = n-Bu, M = Li) readily isomerizes even at 40 1C in
THF.8 In 2006, we developed a new type of configurationally stable (Z)-enethiol equivalent, silver(I) (Z)-b-alkylvinylthiolate 1b, by utilizing an unusual vinylic SN2 reaction of (E)-b-alkylvinyl-l3-iodane with thiobenzamide, followed by hydrolysis with silver acetate (Scheme 2).9,10 Enethiolate 1b is stable upon storage in a refrigerator (4 1C) for 3 months, but it is light-sensitive, and its reactivity is only moderate. For example, (1) 50% degradation of 1b was observed at room temperature after 5 days without light protection; (2) slow isomerization of 1b occurs in solution in the absence of a radical scavenger; (3) with less reactive substrates, addition of n-Bu4NI or LiI is necessary to increase the nucleophilicity of sulfur and/or to activate electrophiles, and this may lead to side-reactions (vide infra). Herein, we report the first synthesis and characterization of gold(I) enethiolates. These are the most robust and practically convenient enethiolates currently available, and enable straightforward installation of a (Z)-enethiol unit in functional molecules. Furthermore, PPh3- and N-heterocyclic carbene (NHC)-coordinated gold(I) enethiolates function as much better nucleophiles than the corresponding silver(I) enethiolates. Gold(I) enethiolates are
Scheme 1 group.
Biologically active b-lactam antibiotics containing a (Z)-vinylthio
Scheme 2
Synthesis and reaction of (Z)-silver enethiolate 1b.
a
Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-12 Bunkyo-ku, Hongo, Tokyo, 113-0033, Japan. E-mail: [email protected] b Advanced Elements Chemistry Research Team, RIKEN Center for Sustainable Resource Science, and Elements Chemistry Laboratory, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan c Graduate School of Pharmaceutical Sciences, University of Tokushima, 1-78 Shomachi, Tokushima 770-8505, Japan † Electronic supplementary information (ESI) available: Experimental details, figures, and spectral data. CCDC 1026924 (10a). For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c5cc02000j
This journal is © The Royal Society of Chemistry 2015
Chem. Commun.
View Article Online
Published on 01 April 2015. Downloaded by UNIVERSITY OF NEBRASKA on 13/04/2015 15:21:04.
Communication
thermally stable, photostable, and show high reactivity towards alkyl halides, cyclic enones, and electron-deficient aryl halides under mild reaction conditions. The key to success in the preparation of gold(I) enethiolates 7 was the use of AuCl–tetrahydrothiophene complex 6.11 Exposure of S-vinylthiobenzimidonium salt 5a (1 equiv.) to gold(I) complex 6 in the presence of sodium carbonate (2 equiv.) in THF at room temperature under argon resulted in selective hydrolysis to afford gold(I) enethiolate 7a stereoselectively in 90% yield, along with N,N-dimethylbenzamide (94%) (Scheme 3). Gold(I) enethiolate 7a is soluble in various solvents including dichloromethane, chloroform, benzene, and THF, but exhibits poor solubility in more polar solvents such as methanol, ethyl acetate, DMF, DMSO, and water. Gold(I) thiolates intrinsically adopt an oligomeric structure through intermolecular S Au interactions.12 ESI-MS spectra indicated that 7a is prone to adopt dimer and trimer forms (Fig. S1, ESI†), which might account for the reduced solubility in polar solvents. It is noteworthy that 7a showed a much higher photostability than silver enethiolate 1b, and was stable upon bench-top storage for at least 20 days without protection from light (Fig. 1). The bond of the Au(I) ion with the thiolate anion is much stronger than that of the Ag(I) ion (the bond dissociation energy of Au–S is 100 kcal mol1 and that of Ag–S is 51.9 kcal mol1),13 which is consistent with the higher stability of gold(I) thiolate 7a. The strong Au–S interaction enhances the thermal stability and photostability of the enethiolate ion, but might cause a decrease in the reactivity. We envisioned that addition of electron-donating ligands such as triphenylphosphine (PPh3) and NHCs, which form stable 1 : 1 complexes simply upon mixing with 7a at ambient temperature, would increase the nucleophilicity via trans influence and stereoelectronic effects (Scheme 4).14 Complexes 8a–10a showed higher solubility than parent 7a in common organic solvents, such as ethyl acetate and methanol. The increased solubility can be attributed to inhibition of
Scheme 3
ChemComm
Scheme 4
Synthesis of gold(I) (Z)-enethiolate–ligand complexes.
aggregation via intermolecular Au S interaction. The 1 : 1 complex between 7a and PPh3 is predominant in a CDCl3 solution, as indicated by the Job plot of the 13C NMR data (Fig. S2, ESI†). The binding constant was measured to be Ka = 1.8 104 M1 by means of 13C NMR spectroscopic titration at room temperature (Fig. S3, ESI†). Complexation clearly increases the configurational stability of these compounds, and no isomerization of (Z)-enethiolate 8a was observed even after 20 days in CDCl3 at room temperature in the presence of TEMPO (0.1 equiv.).15 The formation of NHC adduct 10a was unambiguously confirmed by X-ray diffraction analysis (Fig. 2).16 The structure contains one carbene ligand in the gold(I) center at the side opposite to the sulfur atom of 10a, with a near-linear S1–Au1– C11 triad (178.261). The thiolate ligand in 10a is tightly bound to the gold(I) center with an Au1–S1 distance of 2.2883 Å, which is slightly longer than the predicted sum of covalent radii (2.27 Å). The CNHC– Au bond length of 2.018 Å in 10a is slightly longer than that observed in the corresponding chloride complex (1.993 Å), which probably reflects a stronger trans influence of the thiolate anion.17 The Au–S and Au–C bond lengths are comparable to those observed in the thioglucoside–Au(I)–NHC complex.18 It is noteworthy that no intermolecular gold gold interaction (o3.2 Å) was observed in the crystal packing structure of 10a.19 We have reported that silver(I) enethiolate shows moderate reactivity towards various alkyl halides. For example, silver(I) enethiolate 1b underwent nucleophilic substitution with methyl iodide (10 equiv.) in dichloromethane at room temperature to
Synthesis of gold (Z)-enethiolate 7.
Fig. 1 Stability differences between silver(I) enethiolate 1b (open circle) and gold(I) enethiolate 7a (filled circle).
Chem. Commun.
Fig. 2 ORTEP drawing of gold enethiolate-6–Mes complex 10a with thermal ellipsoids at 50% probability. Selected bond lengths (Å) and angles (deg): Au1–S1 2.2883(12), Au1–C11 2.018(2), S1–C1 1.774(5), C1–C2 1.354(7), S1–Au1–C11 178.26(11), Au1–S1–C1 102.21(15), S1–C1–C2 123.5(4).
This journal is © The Royal Society of Chemistry 2015
View Article Online
ChemComm
Published on 01 April 2015. Downloaded by UNIVERSITY OF NEBRASKA on 13/04/2015 15:21:04.
Table 1
Communication
Alkylation of gold (Z)-enethiolates
Entry
Thiolate
RI
Time (h)
Yielda (%)
11 Z : Eb
1 2 3 4 5c 6c 7 8c 9 10 11c 12 13 14
7a 8a 9a 10a 9a 10a 8a 8a 8a 10a 10a 8a 8a 8a
MeI MeI MeI MeI MeI MeI EtI EtI i-PrI i-PrI i-PrI CH2QCHCH2Br PhCH2Br PhCOCH2Br
7 3 0.5 0.5 0.5 0.5 24 24 48 48 48 12 4 4
0 11a 77 11a 79 11a 79 11a 95 11a 93 11a 73 11b 82 11b 33 11c 63 11c 93 11c 97 11d 77 11e 89 11f
— 96 : 4 99 : 1 499 : 1 98 : 2 99 : 1 78 : 22 94 : 6 91 : 9 92 : 8 91 : 9 96 : 4 95 : 5 94 : 6
a Isolated yields. b Determined by 1H NMR analyses. c 0.1 equiv. of TEMPO was added.
give a regioisomeric mixture of methyl vinyl sulfide 11a (R = Me, Z : E = 92 : 8) in 65% yield.10 In contrast, gold(I) enethiolate 7a was inert under similar conditions (Table 1, entry 1). However, phosphine and NHC-treated 8a–10a reacted smoothly with alkyl iodide to afford (Z)-vinyl sulfide 11 in high yields (entries 2–11). The Z-selectivity was generally very high (491%), and the use of TEMPO as an additive improved the yield and/or selectivity (entries 5, 6, 8, and 11).20 Complexes 9a and 10a with stronger trans-influencing NHC ligands showed higher reactivity toward nucleophiles than phosphine complex 8a. For example, branched isopropyl iodide underwent nucleophilic substitution smoothly with 10a in high yield (entry 10), while 8a was less reactive under similar conditions (entry 9). Allyl/benzyl bromide and 20 -bromoacetophenone could be employed in these reactions (entries 12–14), and the yields and stereo-/regioselectivities of (Z)-vinyl sulfides 11d–f were very high. It should be noted that gold(I) enethiolate 10a serves as a highly selective nucleophile for alkyl iodide. In contrast, ammonium (Z)-vinylthiolate 12 generated in situ from silver(I) enethiolate 1a undergoes the SN2 reaction with isopropyl iodide to form the corresponding sulfide 11c in low yield, accompanied by the formation of dithioacetal 13 (22%) from solvent dichloromethane (Scheme 5).10 However, gold(I) enethiolate 10a selectively reacted with isopropyl iodide to afford sulfide 11c in high yield (93%), and the formation of dithioacetal 13 was negligibly small. The superior reactivity of gold(I) enethiolate with isopropyl iodide is probably due to the more favorable Au(I) I interaction, which increases the leaving group ability of the iodine atom in isopropyl iodide.21 Similar gold(I)–halogen interaction-assisted enhancement of the reactivity of gold(I) enethiolate 10a was observed in arylation with 2,4-dinitrohalobenzenes (Scheme 6). Reaction of equimolar 2,4-dinitrohalobenzenes 14a–c and enethiolate 10a at room temperature resulted in aromatic nucleophilic substitution (SNAr) at the halogen ipso position, affording the corresponding
This journal is © The Royal Society of Chemistry 2015
Scheme 5 Competitive alkylation of metal thiolates between isopropyl iodide and dichloromethane.
aryl vinyl sulfide 15 in high yield with excellent stereoselectivity, while 9a was less reactive.22 In the SNAr reaction of 2,4-dinitrohalobenzene with ammonium thiophenoxide (PhSBu4N+), the reactivity of halobenzenes has been reported to decrease monotonically in the order F 4 Cl 4 Br 4 I.23 Interestingly, the present SNAr reaction with gold(I) enethiolate showed completely the opposite reactivity in terms of the halogen leaving ability. The difference is due, at least in part, to the coordination of the Au(I) ion to the halogen atom, increasing the positive charge on the ipso carbon atom of 14 (Scheme 7).24 A similar mechanism has been proposed in diaryl ether synthesis by the reaction of alkali metal phenoxide with haloarenes.25 These observations suggest that the Au(I) ion can transform the intrinsic reactivity of ‘‘(naked) thiolate anion’’ with electrophiles. We have reported that silver(I) enethiolate 1b smoothly undergoes Michael addition with 2-cyclohexen-1-one 15b, and the reaction is accelerated by the presence of lithium iodide.10 In situ-generated gold(I) enethiolate 8a could also be used in Michael addition with cyclic enones 15a–c in the presence of lithium iodide. In these reactions, the lithium cation functions as a Lewis acid; the use of n-Bu4NI or NaI instead of lithium iodide did not afford 16b at all (Scheme 8). In conclusion, we have developed an efficient method for the synthesis of a bench-top-stable (Z)-enethiol equivalent, i.e., gold(I) (Z)-enethiolates, which serve as efficient nucleophiles
Scheme 6
SNAr reaction of 2,4-dinitrohalobenzenes with gold(I) enethiolates.
Scheme 7 A possible transition structure for the SNAr reaction of enethiolate 10a.
Chem. Commun.
View Article Online
Communication
Published on 01 April 2015. Downloaded by UNIVERSITY OF NEBRASKA on 13/04/2015 15:21:04.
Scheme 8 Michael addition of enethiolate 8a generated in situ toward cycloalkenone.
for the SN2 reaction, the SNAr reaction, and Michael addition, affording a variety of (Z)-vinyl sulfides. Thus, the gold(I) ion not only tames the configurationally labile enethiolate moiety, but also changes its reactivity toward electrophiles such as alkyl halides and aryl halides.
Notes and references 1 (a) G. Brooks, K. Coleman, J. S. Davies and P. A. Hunter, J. Antibiot., 1988, 41, 892; (b) S. Nishimura, N. Yasuda, H. Sasaki, K. Kawabata, L. Sakane and T. Takaya, J. Antibiot., 1990, 43, 1160; (c) C. Yokoo, M. Goi, A. Onodera, H. Fukushima and T. Nagate, J. Antibiot., 1991, 44, 1422. 2 For leukotriene inhibitor containing (Z)-vinyl sulfide, see: E. J. Corey, J. R. Cashman, T. M. Eckrich and D. R. Corey, J. Am. Chem. Soc., 1985, 107, 713. 3 (a) O. P. Strausz, T. Hikida and H. E. Gunning, Can. J. Chem., 1965, 43, 717; (b) W. Ando, T. Ohtaki, T. Suzuki and Y. Kabe, J. Am. Chem. Soc., 1991, 113, 7782; (c) A. E. Bruno, R. P. Steer and P. G. Mezey, J. Comput. Chem., 1983, 4, 104; (d) X.-M. Zhang, D. Malick and G. A. Petersson, J. Org. Chem., 1998, 63, 5314; (e) A. Basheer and Z. Rappoport, Org. Biomol. Chem., 2008, 6, 1071. 4 (a) F. W. Stacey and J. F. Harris, J. Am. Chem. Soc., 1963, 85, 963; (b) E. Campaigne and R. D. Moss, J. Am. Chem. Soc., 1954, 76, 1269; (c) T. Seltzer and Z. Rappoport, J. Org. Chem., 1996, 61, 5462. 5 M. Giffard and I. Leaute, J. Chem. Res., 1990, 320. 6 A.-M. Le Nocher and P. Metzner, Tetrahedron Lett., 1992, 41, 6151. 7 J. O’Donnell, S. P. Singh, T. A. Metcalf and A. L. Schwan, Eur. J. Org. Chem., 2009, 547. 8 A. L. Schwan and M. D. Refvik, Synlett, 1998, 96. 9 M. Ochiai, S. Yamamoto, T. Suefuji and D.-W. Chen, Org. Lett., 2001, 3, 2753. 10 M. Ochiai, M. Hirobe and K. Miyamoto, J. Am. Chem. Soc., 2006, 128, 9046. 11 R. Uson, A. Laguna, M. Laguna, D. A. Briggs, H. H. Murray and J. P. Fackler, Inorg. Synth., 2007, 26, 1. 12 (a) J. A. S. Howell, Polyhedron, 2006, 25, 2993; (b) P. J. Bonasia, D. E. Gindelberger and J. Arnold, Inorg. Chem., 1993, 32, 5126; (c) D. J. LeBlanc and C. J. L. Lock, Acta Crystallogr., 1997, C53, 1765; (d) H. Gronbeck, M. Walter and H. Hakkinen, J. Am. Chem. Soc., 2006, 128, 10268.
Chem. Commun.
ChemComm 13 T. Pradeep, C. Evans, J. Shen and R. G. Cooks, J. Phys. Chem. B, 1999, 103, 5304. 14 (a) A. Pidcock, R. E. Richards and L. M. Venanzi, J. Chem. Soc. A, 1966, 1707; (b) T. G. Appleton, H. C. Clark and L. E. Manzer, Coord. Chem. Rev., 1973, 10, 335; (c) G. Henrici-Olive and S. Olive, Coordination and Catalysis, Verlag Chemie, Weinheim, 1977; (d) K. B. Yatsimirskii, Pure Appl. Chem., 1974, 38, 341. 15 Isomerization of 8a in CDCl3 at 23 1C under argon has been investigated (Fig. S4, ESI†). In the presence of 0.1 equiv. of TEMPO, no significant isomerization of 8a was observed even after 1 month, whereas without TEMPO, about 10% E-isomer was detected. 16 Crystal data for 10a: C32H47AuN2S, colorless prisms with dimensions of 0.20 0.20 0.10 mm3, monoclinic, P1% (no. 2), a = 9.6005(4), b = 11.3245(5), c = 15.2126(7) Å, a = 74.934(2), b = 82.830(2), g = 77.842(2)1 V = 1556.9(2) Å3, Z = 2, Dcalcd = 1.469 g cm3. Data were collected on a Rigaku RAXIS-RAPID Imaging Plate diffractometer with MoKa radiation (l = 0.71075 Å) at T = 93 K, 2ymax = 54.91, 24 548 reflections were measured, of which 7077 were unique (Rint = 0.0321), m = 48.296 cm1. The structure was solved by heavy-atom Patterson methods26a and expanded using Fourier techniques,26b R = 0.027, Rw = 0.1063. Hydrogen atoms were included but not refined. CCDC 1026924. 17 J. A. Kovacs and L. M. Brines, Acc. Chem. Res., 2007, 40, 501. 18 M. V. Baker, P. J. Barnard, S. J. Berners-Prins, S. K. Brayshaw, J. L. Hickey, B. W. Skelton and A. H. White, J. Organomet. Chem., 2005, 690, 5625. 19 H. Schmidbaur, Chem. Soc. Rev., 1995, 24, 391. 20 TEMPO probably slows down the rate of isomerization and decomposition of gold thiolates under the reaction conditions. We have reported that a catalytic amount of TEMPO dramatically inhibits the isomerization and decomposition of silver enethiolate 1b under argon. See ref. 10 and 15. 21 A stable gold(I) iodide complex has been reported. Z. Tang, A. P. Litvinchuk, H.-Y. Lee and A. M. Guloy, Inorg. Chem., 1998, 37, 4752. 22 In this case, radical intervention (SRN1 mechanism) can be ruled out, because TEMPO does not inhibit the reaction. 23 W. P. Reeves, T. C. Bothwell and J. A. Rudis, Synth. Commun., 1982, 12, 1071. 24 Although gold(I) species generally favor a dicoordinated structure with linear L–Au–L geometry, some tricoordinated Au(I) species have been reported. For the X-ray structure of AuCl(PPh3)2, see: M. Khan, C. Oldham and D. G. Tuck, Can. J. Chem., 1981, 59, 2714. 25 G. O. Jones, A. A. Somaa, J. M. O’Brian, H. Albishi, H. A. Al-Megrem, A. M. Alabdulrahman, F. D. Alsewailem, J. L. Hedrick, J. E. Rice and H. W. Horn, J. Org. Chem., 2013, 78, 5436. 26 (a) PATTY: P. T. Beurskens, G. Admiraal, W. P. Bosman, R. de Gelder, R. Israel and J. M. Smiths, The DIRDIF-94 Program System, Technical Report of Crystallography Laboratory, University of Nijmegen, The Netherlands, 1994; (b) DIRDIF99: P. T. Beurskens, G. Admiraal, G. Beurskens, W. P. Bosman, R. de Gelder, R. Israel and J. M. M. Smits, The DIRDIF-99 Program System, Technical Report of Crystallography Laboratory, University of Nijmegen, The Netherlands, 1999.
This journal is © The Royal Society of Chemistry 2015
Published on 01 April 2015. Downloaded by UNIVERSITY OF NEBRASKA on 13/04/2015 15:21:04.
COMMUNICATION
Cite this: DOI: 10.1039/c5cc02000j Received 9th March 2015, Accepted 1st April 2015
View Journal
Stereoselective synthesis and reaction of gold(I) (Z)-enethiolates† Kazunori Miyamoto,*ab Masaya Hirobe,c Masanobu Uchiyamaab and Masahito Ochiaic
DOI: 10.1039/c5cc02000j www.rsc.org/chemcomm
Bench-top-storable (Z)-enethiol reagents: gold (Z)-1-decenylthiolates were synthesized stereoselectively in high yields. They are stable upon storage at room temperature without protection from light, and react smoothly with various alkyl halides, a,b-unsaturated ketones, and electron-deficient aryl halides with excellent stereoselectivity.
The (Z)-vinylthio moiety is an important functional group in organic synthesis and medicinal chemistry, being present in many pharmaceutically important compounds (Scheme 1).1,2 For example, a vinylthio functionality is present as a side chain in clavulanic acid derivatives, which show b-lactamase-inhibitory activity,1a and cephem derivatives, which exhibit broad-spectrum antibacterial activities.1b In both cases, the (Z)-isomers show greater activity than the (E)-isomers. The parent enethiols (RCHQCHSH) 1 are fairly tautomerically stable,3 but in general, they are thermally unstable and readily undergo dimerization to give dithiohemiacetals or divinylsulfides even at room temperature.4 Therefore, regio- and stereoselective synthesis of functionalized vinylthio moieties remains a challenging issue in organic synthesis, and only limited success has been achieved by using silyl vinyl sulfides as precursors.5,6 In contrast, some heavier-metal enethiolates are less prone to dimerization. For example, cesium (Z)-enethiolate generated in situ at low temperature reacts with alkyl halides to afford (Z)-vinyl sulfides with high stereoselectivity (up to 98 : 2).7 However, the use of a harder counter cation such as the lithium ion results in configurational lability: enethiolate 1a (R = n-Bu, M = Li) readily isomerizes even at 40 1C in
THF.8 In 2006, we developed a new type of configurationally stable (Z)-enethiol equivalent, silver(I) (Z)-b-alkylvinylthiolate 1b, by utilizing an unusual vinylic SN2 reaction of (E)-b-alkylvinyl-l3-iodane with thiobenzamide, followed by hydrolysis with silver acetate (Scheme 2).9,10 Enethiolate 1b is stable upon storage in a refrigerator (4 1C) for 3 months, but it is light-sensitive, and its reactivity is only moderate. For example, (1) 50% degradation of 1b was observed at room temperature after 5 days without light protection; (2) slow isomerization of 1b occurs in solution in the absence of a radical scavenger; (3) with less reactive substrates, addition of n-Bu4NI or LiI is necessary to increase the nucleophilicity of sulfur and/or to activate electrophiles, and this may lead to side-reactions (vide infra). Herein, we report the first synthesis and characterization of gold(I) enethiolates. These are the most robust and practically convenient enethiolates currently available, and enable straightforward installation of a (Z)-enethiol unit in functional molecules. Furthermore, PPh3- and N-heterocyclic carbene (NHC)-coordinated gold(I) enethiolates function as much better nucleophiles than the corresponding silver(I) enethiolates. Gold(I) enethiolates are
Scheme 1 group.
Biologically active b-lactam antibiotics containing a (Z)-vinylthio
Scheme 2
Synthesis and reaction of (Z)-silver enethiolate 1b.
a
Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-12 Bunkyo-ku, Hongo, Tokyo, 113-0033, Japan. E-mail: [email protected] b Advanced Elements Chemistry Research Team, RIKEN Center for Sustainable Resource Science, and Elements Chemistry Laboratory, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan c Graduate School of Pharmaceutical Sciences, University of Tokushima, 1-78 Shomachi, Tokushima 770-8505, Japan † Electronic supplementary information (ESI) available: Experimental details, figures, and spectral data. CCDC 1026924 (10a). For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c5cc02000j
This journal is © The Royal Society of Chemistry 2015
Chem. Commun.
View Article Online
Published on 01 April 2015. Downloaded by UNIVERSITY OF NEBRASKA on 13/04/2015 15:21:04.
Communication
thermally stable, photostable, and show high reactivity towards alkyl halides, cyclic enones, and electron-deficient aryl halides under mild reaction conditions. The key to success in the preparation of gold(I) enethiolates 7 was the use of AuCl–tetrahydrothiophene complex 6.11 Exposure of S-vinylthiobenzimidonium salt 5a (1 equiv.) to gold(I) complex 6 in the presence of sodium carbonate (2 equiv.) in THF at room temperature under argon resulted in selective hydrolysis to afford gold(I) enethiolate 7a stereoselectively in 90% yield, along with N,N-dimethylbenzamide (94%) (Scheme 3). Gold(I) enethiolate 7a is soluble in various solvents including dichloromethane, chloroform, benzene, and THF, but exhibits poor solubility in more polar solvents such as methanol, ethyl acetate, DMF, DMSO, and water. Gold(I) thiolates intrinsically adopt an oligomeric structure through intermolecular S Au interactions.12 ESI-MS spectra indicated that 7a is prone to adopt dimer and trimer forms (Fig. S1, ESI†), which might account for the reduced solubility in polar solvents. It is noteworthy that 7a showed a much higher photostability than silver enethiolate 1b, and was stable upon bench-top storage for at least 20 days without protection from light (Fig. 1). The bond of the Au(I) ion with the thiolate anion is much stronger than that of the Ag(I) ion (the bond dissociation energy of Au–S is 100 kcal mol1 and that of Ag–S is 51.9 kcal mol1),13 which is consistent with the higher stability of gold(I) thiolate 7a. The strong Au–S interaction enhances the thermal stability and photostability of the enethiolate ion, but might cause a decrease in the reactivity. We envisioned that addition of electron-donating ligands such as triphenylphosphine (PPh3) and NHCs, which form stable 1 : 1 complexes simply upon mixing with 7a at ambient temperature, would increase the nucleophilicity via trans influence and stereoelectronic effects (Scheme 4).14 Complexes 8a–10a showed higher solubility than parent 7a in common organic solvents, such as ethyl acetate and methanol. The increased solubility can be attributed to inhibition of
Scheme 3
ChemComm
Scheme 4
Synthesis of gold(I) (Z)-enethiolate–ligand complexes.
aggregation via intermolecular Au S interaction. The 1 : 1 complex between 7a and PPh3 is predominant in a CDCl3 solution, as indicated by the Job plot of the 13C NMR data (Fig. S2, ESI†). The binding constant was measured to be Ka = 1.8 104 M1 by means of 13C NMR spectroscopic titration at room temperature (Fig. S3, ESI†). Complexation clearly increases the configurational stability of these compounds, and no isomerization of (Z)-enethiolate 8a was observed even after 20 days in CDCl3 at room temperature in the presence of TEMPO (0.1 equiv.).15 The formation of NHC adduct 10a was unambiguously confirmed by X-ray diffraction analysis (Fig. 2).16 The structure contains one carbene ligand in the gold(I) center at the side opposite to the sulfur atom of 10a, with a near-linear S1–Au1– C11 triad (178.261). The thiolate ligand in 10a is tightly bound to the gold(I) center with an Au1–S1 distance of 2.2883 Å, which is slightly longer than the predicted sum of covalent radii (2.27 Å). The CNHC– Au bond length of 2.018 Å in 10a is slightly longer than that observed in the corresponding chloride complex (1.993 Å), which probably reflects a stronger trans influence of the thiolate anion.17 The Au–S and Au–C bond lengths are comparable to those observed in the thioglucoside–Au(I)–NHC complex.18 It is noteworthy that no intermolecular gold gold interaction (o3.2 Å) was observed in the crystal packing structure of 10a.19 We have reported that silver(I) enethiolate shows moderate reactivity towards various alkyl halides. For example, silver(I) enethiolate 1b underwent nucleophilic substitution with methyl iodide (10 equiv.) in dichloromethane at room temperature to
Synthesis of gold (Z)-enethiolate 7.
Fig. 1 Stability differences between silver(I) enethiolate 1b (open circle) and gold(I) enethiolate 7a (filled circle).
Chem. Commun.
Fig. 2 ORTEP drawing of gold enethiolate-6–Mes complex 10a with thermal ellipsoids at 50% probability. Selected bond lengths (Å) and angles (deg): Au1–S1 2.2883(12), Au1–C11 2.018(2), S1–C1 1.774(5), C1–C2 1.354(7), S1–Au1–C11 178.26(11), Au1–S1–C1 102.21(15), S1–C1–C2 123.5(4).
This journal is © The Royal Society of Chemistry 2015
View Article Online
ChemComm
Published on 01 April 2015. Downloaded by UNIVERSITY OF NEBRASKA on 13/04/2015 15:21:04.
Table 1
Communication
Alkylation of gold (Z)-enethiolates
Entry
Thiolate
RI
Time (h)
Yielda (%)
11 Z : Eb
1 2 3 4 5c 6c 7 8c 9 10 11c 12 13 14
7a 8a 9a 10a 9a 10a 8a 8a 8a 10a 10a 8a 8a 8a
MeI MeI MeI MeI MeI MeI EtI EtI i-PrI i-PrI i-PrI CH2QCHCH2Br PhCH2Br PhCOCH2Br
7 3 0.5 0.5 0.5 0.5 24 24 48 48 48 12 4 4
0 11a 77 11a 79 11a 79 11a 95 11a 93 11a 73 11b 82 11b 33 11c 63 11c 93 11c 97 11d 77 11e 89 11f
— 96 : 4 99 : 1 499 : 1 98 : 2 99 : 1 78 : 22 94 : 6 91 : 9 92 : 8 91 : 9 96 : 4 95 : 5 94 : 6
a Isolated yields. b Determined by 1H NMR analyses. c 0.1 equiv. of TEMPO was added.
give a regioisomeric mixture of methyl vinyl sulfide 11a (R = Me, Z : E = 92 : 8) in 65% yield.10 In contrast, gold(I) enethiolate 7a was inert under similar conditions (Table 1, entry 1). However, phosphine and NHC-treated 8a–10a reacted smoothly with alkyl iodide to afford (Z)-vinyl sulfide 11 in high yields (entries 2–11). The Z-selectivity was generally very high (491%), and the use of TEMPO as an additive improved the yield and/or selectivity (entries 5, 6, 8, and 11).20 Complexes 9a and 10a with stronger trans-influencing NHC ligands showed higher reactivity toward nucleophiles than phosphine complex 8a. For example, branched isopropyl iodide underwent nucleophilic substitution smoothly with 10a in high yield (entry 10), while 8a was less reactive under similar conditions (entry 9). Allyl/benzyl bromide and 20 -bromoacetophenone could be employed in these reactions (entries 12–14), and the yields and stereo-/regioselectivities of (Z)-vinyl sulfides 11d–f were very high. It should be noted that gold(I) enethiolate 10a serves as a highly selective nucleophile for alkyl iodide. In contrast, ammonium (Z)-vinylthiolate 12 generated in situ from silver(I) enethiolate 1a undergoes the SN2 reaction with isopropyl iodide to form the corresponding sulfide 11c in low yield, accompanied by the formation of dithioacetal 13 (22%) from solvent dichloromethane (Scheme 5).10 However, gold(I) enethiolate 10a selectively reacted with isopropyl iodide to afford sulfide 11c in high yield (93%), and the formation of dithioacetal 13 was negligibly small. The superior reactivity of gold(I) enethiolate with isopropyl iodide is probably due to the more favorable Au(I) I interaction, which increases the leaving group ability of the iodine atom in isopropyl iodide.21 Similar gold(I)–halogen interaction-assisted enhancement of the reactivity of gold(I) enethiolate 10a was observed in arylation with 2,4-dinitrohalobenzenes (Scheme 6). Reaction of equimolar 2,4-dinitrohalobenzenes 14a–c and enethiolate 10a at room temperature resulted in aromatic nucleophilic substitution (SNAr) at the halogen ipso position, affording the corresponding
This journal is © The Royal Society of Chemistry 2015
Scheme 5 Competitive alkylation of metal thiolates between isopropyl iodide and dichloromethane.
aryl vinyl sulfide 15 in high yield with excellent stereoselectivity, while 9a was less reactive.22 In the SNAr reaction of 2,4-dinitrohalobenzene with ammonium thiophenoxide (PhSBu4N+), the reactivity of halobenzenes has been reported to decrease monotonically in the order F 4 Cl 4 Br 4 I.23 Interestingly, the present SNAr reaction with gold(I) enethiolate showed completely the opposite reactivity in terms of the halogen leaving ability. The difference is due, at least in part, to the coordination of the Au(I) ion to the halogen atom, increasing the positive charge on the ipso carbon atom of 14 (Scheme 7).24 A similar mechanism has been proposed in diaryl ether synthesis by the reaction of alkali metal phenoxide with haloarenes.25 These observations suggest that the Au(I) ion can transform the intrinsic reactivity of ‘‘(naked) thiolate anion’’ with electrophiles. We have reported that silver(I) enethiolate 1b smoothly undergoes Michael addition with 2-cyclohexen-1-one 15b, and the reaction is accelerated by the presence of lithium iodide.10 In situ-generated gold(I) enethiolate 8a could also be used in Michael addition with cyclic enones 15a–c in the presence of lithium iodide. In these reactions, the lithium cation functions as a Lewis acid; the use of n-Bu4NI or NaI instead of lithium iodide did not afford 16b at all (Scheme 8). In conclusion, we have developed an efficient method for the synthesis of a bench-top-stable (Z)-enethiol equivalent, i.e., gold(I) (Z)-enethiolates, which serve as efficient nucleophiles
Scheme 6
SNAr reaction of 2,4-dinitrohalobenzenes with gold(I) enethiolates.
Scheme 7 A possible transition structure for the SNAr reaction of enethiolate 10a.
Chem. Commun.
View Article Online
Communication
Published on 01 April 2015. Downloaded by UNIVERSITY OF NEBRASKA on 13/04/2015 15:21:04.
Scheme 8 Michael addition of enethiolate 8a generated in situ toward cycloalkenone.
for the SN2 reaction, the SNAr reaction, and Michael addition, affording a variety of (Z)-vinyl sulfides. Thus, the gold(I) ion not only tames the configurationally labile enethiolate moiety, but also changes its reactivity toward electrophiles such as alkyl halides and aryl halides.
Notes and references 1 (a) G. Brooks, K. Coleman, J. S. Davies and P. A. Hunter, J. Antibiot., 1988, 41, 892; (b) S. Nishimura, N. Yasuda, H. Sasaki, K. Kawabata, L. Sakane and T. Takaya, J. Antibiot., 1990, 43, 1160; (c) C. Yokoo, M. Goi, A. Onodera, H. Fukushima and T. Nagate, J. Antibiot., 1991, 44, 1422. 2 For leukotriene inhibitor containing (Z)-vinyl sulfide, see: E. J. Corey, J. R. Cashman, T. M. Eckrich and D. R. Corey, J. Am. Chem. Soc., 1985, 107, 713. 3 (a) O. P. Strausz, T. Hikida and H. E. Gunning, Can. J. Chem., 1965, 43, 717; (b) W. Ando, T. Ohtaki, T. Suzuki and Y. Kabe, J. Am. Chem. Soc., 1991, 113, 7782; (c) A. E. Bruno, R. P. Steer and P. G. Mezey, J. Comput. Chem., 1983, 4, 104; (d) X.-M. Zhang, D. Malick and G. A. Petersson, J. Org. Chem., 1998, 63, 5314; (e) A. Basheer and Z. Rappoport, Org. Biomol. Chem., 2008, 6, 1071. 4 (a) F. W. Stacey and J. F. Harris, J. Am. Chem. Soc., 1963, 85, 963; (b) E. Campaigne and R. D. Moss, J. Am. Chem. Soc., 1954, 76, 1269; (c) T. Seltzer and Z. Rappoport, J. Org. Chem., 1996, 61, 5462. 5 M. Giffard and I. Leaute, J. Chem. Res., 1990, 320. 6 A.-M. Le Nocher and P. Metzner, Tetrahedron Lett., 1992, 41, 6151. 7 J. O’Donnell, S. P. Singh, T. A. Metcalf and A. L. Schwan, Eur. J. Org. Chem., 2009, 547. 8 A. L. Schwan and M. D. Refvik, Synlett, 1998, 96. 9 M. Ochiai, S. Yamamoto, T. Suefuji and D.-W. Chen, Org. Lett., 2001, 3, 2753. 10 M. Ochiai, M. Hirobe and K. Miyamoto, J. Am. Chem. Soc., 2006, 128, 9046. 11 R. Uson, A. Laguna, M. Laguna, D. A. Briggs, H. H. Murray and J. P. Fackler, Inorg. Synth., 2007, 26, 1. 12 (a) J. A. S. Howell, Polyhedron, 2006, 25, 2993; (b) P. J. Bonasia, D. E. Gindelberger and J. Arnold, Inorg. Chem., 1993, 32, 5126; (c) D. J. LeBlanc and C. J. L. Lock, Acta Crystallogr., 1997, C53, 1765; (d) H. Gronbeck, M. Walter and H. Hakkinen, J. Am. Chem. Soc., 2006, 128, 10268.
Chem. Commun.
ChemComm 13 T. Pradeep, C. Evans, J. Shen and R. G. Cooks, J. Phys. Chem. B, 1999, 103, 5304. 14 (a) A. Pidcock, R. E. Richards and L. M. Venanzi, J. Chem. Soc. A, 1966, 1707; (b) T. G. Appleton, H. C. Clark and L. E. Manzer, Coord. Chem. Rev., 1973, 10, 335; (c) G. Henrici-Olive and S. Olive, Coordination and Catalysis, Verlag Chemie, Weinheim, 1977; (d) K. B. Yatsimirskii, Pure Appl. Chem., 1974, 38, 341. 15 Isomerization of 8a in CDCl3 at 23 1C under argon has been investigated (Fig. S4, ESI†). In the presence of 0.1 equiv. of TEMPO, no significant isomerization of 8a was observed even after 1 month, whereas without TEMPO, about 10% E-isomer was detected. 16 Crystal data for 10a: C32H47AuN2S, colorless prisms with dimensions of 0.20 0.20 0.10 mm3, monoclinic, P1% (no. 2), a = 9.6005(4), b = 11.3245(5), c = 15.2126(7) Å, a = 74.934(2), b = 82.830(2), g = 77.842(2)1 V = 1556.9(2) Å3, Z = 2, Dcalcd = 1.469 g cm3. Data were collected on a Rigaku RAXIS-RAPID Imaging Plate diffractometer with MoKa radiation (l = 0.71075 Å) at T = 93 K, 2ymax = 54.91, 24 548 reflections were measured, of which 7077 were unique (Rint = 0.0321), m = 48.296 cm1. The structure was solved by heavy-atom Patterson methods26a and expanded using Fourier techniques,26b R = 0.027, Rw = 0.1063. Hydrogen atoms were included but not refined. CCDC 1026924. 17 J. A. Kovacs and L. M. Brines, Acc. Chem. Res., 2007, 40, 501. 18 M. V. Baker, P. J. Barnard, S. J. Berners-Prins, S. K. Brayshaw, J. L. Hickey, B. W. Skelton and A. H. White, J. Organomet. Chem., 2005, 690, 5625. 19 H. Schmidbaur, Chem. Soc. Rev., 1995, 24, 391. 20 TEMPO probably slows down the rate of isomerization and decomposition of gold thiolates under the reaction conditions. We have reported that a catalytic amount of TEMPO dramatically inhibits the isomerization and decomposition of silver enethiolate 1b under argon. See ref. 10 and 15. 21 A stable gold(I) iodide complex has been reported. Z. Tang, A. P. Litvinchuk, H.-Y. Lee and A. M. Guloy, Inorg. Chem., 1998, 37, 4752. 22 In this case, radical intervention (SRN1 mechanism) can be ruled out, because TEMPO does not inhibit the reaction. 23 W. P. Reeves, T. C. Bothwell and J. A. Rudis, Synth. Commun., 1982, 12, 1071. 24 Although gold(I) species generally favor a dicoordinated structure with linear L–Au–L geometry, some tricoordinated Au(I) species have been reported. For the X-ray structure of AuCl(PPh3)2, see: M. Khan, C. Oldham and D. G. Tuck, Can. J. Chem., 1981, 59, 2714. 25 G. O. Jones, A. A. Somaa, J. M. O’Brian, H. Albishi, H. A. Al-Megrem, A. M. Alabdulrahman, F. D. Alsewailem, J. L. Hedrick, J. E. Rice and H. W. Horn, J. Org. Chem., 2013, 78, 5436. 26 (a) PATTY: P. T. Beurskens, G. Admiraal, W. P. Bosman, R. de Gelder, R. Israel and J. M. Smiths, The DIRDIF-94 Program System, Technical Report of Crystallography Laboratory, University of Nijmegen, The Netherlands, 1994; (b) DIRDIF99: P. T. Beurskens, G. Admiraal, G. Beurskens, W. P. Bosman, R. de Gelder, R. Israel and J. M. M. Smits, The DIRDIF-99 Program System, Technical Report of Crystallography Laboratory, University of Nijmegen, The Netherlands, 1999.
This journal is © The Royal Society of Chemistry 2015
